We propose to continue investigating neuropathological correlates of affective disorders using paradigms in which event-related potentials (ERPs) and behavioral responses are concurrently obtained. An early finding that the P300 component is smaller, but of normal latency, in patients meeting the research diagnostic criteria for major depressive disorder than age- and educationally-matched controls will be further evaluated. Single-trial ERP analysis, and a closer examination of the effect of sequential probabilities, will be used to examine the possibility that smaller P300s are due to latency jitter, or altered subjective expectancies in the depressed patients. The relationship between P300 latency and RT will be examined to clarify the locus of slower behavioral responses in the depressed patients. Patients are clinically evaluated using the Schedule for Affective Disorders and Schizophrenia. The clinical and ERP evaluation occurs after a two-week drug washout period, and is repeated after a course of anti-depressant therapy. The data will be analyzed to determine whether any baseline ERP or clinical measures predict treatment responsiveness and whether any ERP abnormalities return to normal after clinical improvement.